Chlordecone (Kepone) is a chlorinated hydrocarbon insecticide. One of the most severe and consistent neurological symptoms observed in exposed workers or laboratory animals was tremor. The purpose of this project was: a) to characterize the effects of chlordecone on the brain neurotransmitter systems such as biogenic amines, acetylcholine (Ach) and amino acid transmitters by measuring the rate of turnover of these neurotransmitters and to examine the neurochemical effects of chlordecone on hypothalamo-pituitary-adrenal function by determining the plasma levels of ACTH and corticosterone. b) To evaluate the contribution of each neurotransmitter system or hypothalamo-pituitary-adrenal-axis in the tremorigenesis of chlordecone. A single injection of chlordecone caused robust increases in the turnover rate of 5HT and NE, whereas the turnover of DA, Ach and GABA remained unaltered. The steady state concentrations of amino acid transmitters were also not affected. These results suggest the possible involvement of 5HT and NE in the tremorigenesis of chlordecone. This hypothesis was further supported by the finding that BC-105 (a serotonin receptor blocker) and phenoxybenzamine (an alpha adrenergic receptor) significantly attenuated chlordecone-elicited tremor. Chlordecone also caused a great activation of pituitary-adrenal function. A robust increase in the plasma levels of ACTH and corticosterone was found 2 hr after a single injection of chlordecone (75 mg/kg; i.p.). The hypertropic effect of chlordecone on the adrenal and the pituitary was further confirmed by the morphological studies both at the light and the electron microscope levels. However, the possible link between the change in pituitary-adrenal function and chlordecone-elicited behavioral alterations such as tremor or hyperexcitability remains to be studied. For future studies, we plan to examine the possibility that chlordecone, like DDT, may exert its neurochemical or behavioral effects by acting on the sodium channel of the neuronal membrane.